The receptor for epidermal growth factor (EGF) in murine 3T3 cells has been identified as a protein of approximately 185,000 daltons. We propose to isolate the receptor, characterize it biochemically, make antibodies to it, and assess its disposition in the membrane. Preliminary studies show that receptor is degraded in the lysosomes upon down regulation. We have produced both EGF-polyhema beads and ferritin EGF for ultrastructural studies to examine the course of events terminating with degradation. We have reproduced the studies of Whittenberger and Glaser which show that a plasma membrane preparation can block the action of serum in the stimulation of thymidine uptake into DNA, and have shown that this same preparation can block the EFG-induced stimulation of DNA synthesis. These studies will be extended to see if this effect is specific for holding cells in Go, and to attempt to ascertain the mechanism of this "contact inhibition" phenomenon. Studies will also be initiated to search for a factor in EGF stimulated cells which can stimulate macromolecular synthesis in isolated nuclei. We have also succeeded in affinity labeling the receptor for insulin in IM9 cells and are determining its fate on down regulation. Attempts are being made to identify the receptors for: enkephalins, murine leukemia virus antigens, and Rous sarcoma virus antigens.